Department of Head, Neck and Genitourinary Oncology, Harbin Medical University Cancer Hospital, Heilongjiang, 150081, China; Department of Oncology, The Second Affiliated Hospital of Shandong First Medical University, Shandong, 271000, China.
Department of Beijing Institute of Hepatology, Beijing You an Hospital, Capital Medical University, Beijing, 100069, China.
J Ethnopharmacol. 2024 Jun 12;327:117994. doi: 10.1016/j.jep.2024.117994. Epub 2024 Mar 2.
Ixeris sonchifolia alias Kudiezi, it was named Ixeris sonchifolia (Bunge) Hance, a synonym for Crepidiastrum sonchifolium (Bunge) Pak & Kawano in the https://www.iplant.cn/. And it was first published in J. Linn. Soc., Bot. 13: 108 (1873), which was named Ixeris sonchifolia (Maxim.) Hance in the MPNS (http://mpns.kew.org). As a widely distributed medicinal and edible wild plant, it possesses unique bitter-cold characteristics and constituents with various pharmacological activities. Its main antitumor substances, same as artemisinin and paclitaxel, are classified as terpenoids and have become research foci in recent years. However, its specific biological activity and role in antitumor treatment remain largely unclear.
This study aimed to elucidate the molecular targets and potential mechanisms of hepatocellular carcinoma apoptosis induced by Ixeris sonchifolia.
We used network pharmacology methods to analyze and screen the active ingredients and possible underlying mechanisms of Ixeris sonchifolia in treating liver cancer and employed integrative time- and dose-dependent toxicity, transcriptomics, and molecular biology approaches to comprehensively verify the function of Ixeris sonchifolia extract (IsE) in human hepatoblastoma cell (HepG2) apoptosis and its potential mechanism.
A total of 169 common targets were screened by network pharmacology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that IsE inhibited HepG2 cell activity in a time- and dose-dependent manner. Western blot analysis confirmed that IsE promoted HepG2 cell apoptosis by inhibiting the PI3K/AKT signaling pathway and that the PI3K/AKT inhibitor LY294002 also substantially enhanced IsE-induced apoptosis. The PI3K/AKT signaling pathway exhibited significant differences compared to that in the control group.
Combining network pharmacology with experimental verification, IsE inhibited mitochondrial function and the PI3K/AKT pathway while inducing hepatoma cell apoptosis. IsE may have promising potential for liver cancer treatment and chemoprevention.
苦碟子，别名苦荬菜，学名菊科植物苦碟子（抱茎苦荬菜），在 iplant.cn 中被归类为 Crepidiastrum sonchifolium（Bunge）Pak & Kawano 的同义词。它最早于 1873 年在 J. Linn. Soc., Bot. 13: 108 中被命名为 Ixeris sonchifolia（Maxim.）Hance，并在 MPNS（http://mpns.kew.org）中被命名为 Crepidiastrum sonchifolium（Bunge）Pak & Kawano。作为一种广泛分布的药用和食用野生植物，它具有独特的苦寒特性和多种药理活性成分。其主要的抗肿瘤物质与青蒿素和紫杉醇相同，均归类为萜类化合物，近年来已成为研究热点。然而，其具体的生物活性及其在抗肿瘤治疗中的作用仍在很大程度上不明确。
本研究旨在阐明苦碟子诱导肝癌细胞凋亡的分子靶点和潜在机制。
我们采用网络药理学方法分析和筛选苦碟子治疗肝癌的活性成分及可能的作用机制，并采用整合的时间和剂量依赖性毒性、转录组学和分子生物学方法，全面验证苦碟子提取物（IsE）在人肝癌细胞（HepG2）凋亡中的作用及其潜在机制。
通过网络药理学共筛选出 169 个共同靶点，京都基因与基因组百科全书（KEGG）富集分析显示，IsE 呈时间和剂量依赖性抑制 HepG2 细胞活性。Western blot 分析证实，IsE 通过抑制 PI3K/AKT 信号通路促进 HepG2 细胞凋亡，而 PI3K/AKT 抑制剂 LY294002 也能显著增强 IsE 诱导的凋亡。PI3K/AKT 信号通路与对照组相比表现出显著差异。
通过网络药理学与实验验证相结合，IsE 抑制线粒体功能和 PI3K/AKT 通路，诱导肝癌细胞凋亡。IsE 可能在肝癌治疗和化学预防方面具有广阔的应用前景。
